|Causes and Mechanisms of Linear Growth Retardation (International Dietary Energy Consultative Group - IDECG, 1993, 216 pages)|
|The cell biology of bone growth|
The field of bone cell biology is clearly of relevance to the problem of stunting in children, as in the final analysis the cells of the growing long bone are the ultimate 'regulators'. It is the alterations in the functions of these cells that manifests as a reduction in height. Normal longitudinal growth is achieved by the coordinated recruitment, proliferation, differentiation, maturation and eventual death of the cells of growth plate and bone. Cellular activity is closely regulated by endocrine factors acting directly or indirectly, with factors produced locally and stored within the bone and cartilage microenvironment having a critical role in intercellular communication. Disruption of any of these processes can lead to growth disturbances, since it only requires a defect in a single gene to have profound effects. Studies in recent years have shed light on the biochemical and molecular effects of cytokines and growth factors and have shown that these regulatory molecules may mediate the effects of certain hormones important in controlling growth. However, the complex interrelationship of these molecules is still not clear. Notwithstanding, understanding of the mechanisms involved in bone remodelling is increasing, as this area attracts much research because of the high incidence of metabolic bone disease in Western society.
Although studies of adult bone remodelling are of relevance, there is a requirement for increased research directed specifically at the mechanisms of endochondral ossification and its regulation. Longitudinal bone growth is a challenge to the cell biologist, since it is an accelerated cycle of cellular division and differentiation, within which it is not easy to separate events temporally and spatially. In addition, different regulatory mechanisms are probably important at different stages of growth. Another difficulty impeding progress in this field is the lack of appropriate animal models for research. Much information has come from studies involving rodents, and species differences must always be taken into account. Larger mammals such as the growing piglet or the calf are probably more appropriate for the study of postnatal longitudinal growth in man.
If the mechanisms of stunting are to be established at a cellular level, a number of approaches need to be considered. Studies need to be designed using more appropriate animal models, and conditions such as nutritional intake, immunological challenges, chronic intestinal diseases and mechanical loading need to be manipulated. Any effects on longitudinal growth may then be studied temporally and correlated with non-invasive measurements including assays of hormones, cytokines, growth factors and proteins known to regulate their activity. Alterations in growth plate structure and cellular function can be studied in these models in situ using a variety of histological, biochemical and molecular approaches. In vitro studies using cultured growth plate cells, preferably of human origin, are also required for the study of how hormones and cytokines transduce their signals intracellularly.